Andersons pediatric cardiology 1489

Microbiology
ThemajorityofbothnativeandprostheticvalveIEiscausedbygram-positive
bacteria.Thelikelyreasonforthisisthespecificcapacityoftheseorganismsto
bindtosurface-exposedhostreceptorsindenudedinjuredsubendothelialmatrix.
Workhasfurtherelucidatedthecomplexmechanismsandinterrelationships
betweenbacterialbindingandtheformationofbiofilmonhostsubendothelial
surfaces.

StreptococciandEnterococciSpecies
1.Oneofthebest-characterizedbacteriathatcauseIEistheviridans
streptococcus,Streptococcusgordonii.80Themultifunctionalfibrillar
adhesinCshA81canpromotebindingofbacteriatohostcellmatrixby
formingmolecularbridgetohostcellintegrininthesubendothelial
matrix.82
2.InitialbindingofS.gordoniitotwocellsurfaceproteins,Hsaand
plateletadherenceproteinA,mediatesadherenceandactivationof
platelets,mediatingbindingtosubendothelialmatrixproteinsvitronectin
andfibronectin,promotingbiofilmformation.83
3.InEnterococcispp.,commoncausativepathogensinadults,ithasbeen
shownthatthegeneproductofbepA,acarbohydratephosphotransferase
systempermease,islinkedtometabolismofglycosaminoglycan-injured
heartvalves.84

StaphylococcusAureusandOther
Staphylococci
1.S.aureusexpressescellwall–anchored(CWA)proteins.Themost
commongroupofthesearethemicrobialsurfacecomponents
recognizingadhesivematrixmolecules.85Thesearemultifunctional
receptors(suchasclumpingfactorA,fibronectin-bindingproteins)
involvedinadhesiontosubendothelialmatrixproteinssuchas

fibronectinbutarealsoinvolvedintissueinvasion,immunedeviation,
andestablishmentofbiofilmformation.86S.aureusexpressesupto24
differentCWAproteins,whereascoagulase-negativestrainsoften
expressasmallernumberoftheseproteins.Itisverylikelythatthe
increasedvirulenceofS.aureusislikelytoinvolvetheplethoraofCWA
proteinsitisabletoutilizeinhostcellandmatrixinteractions.
2.sarA,aglobalregulatorofmanyS.aureusvirulencefactors,maybe
intricatelyinvolvedinbothregulationofbiofilmproductionbutalso
resistancetooxacillin,viaitsregulationofpenicillin-bindingprotein2b
inmethicillin-resistantstrains,becausesarA-deficientmutantsproduced
significantlylessbiofilmandweremoresusceptibletooxacillinmediatedkillinginexperimentalendocarditismodels.87,88
Theseinvestigationsprovidefurtherrationaletodevelopnovelinterventions,
suchasvaccinesdesignedtoelicitantibodiesthatblockmicrobialhostcell
interactionsorcompoundsdesignedtointerruptmicrobialregulatory
mechanisms.VaccinestrategiestoinduceprotectiveantibodiesinS.aureus89
andEnterococcusfaecalis90havebeenshowntobeeffectiveinexperimental
endocarditis.Inanimalmodels,vaccinationstrategiestoinduceantibodytoHsa
andplateletadherenceproteinAprotectedagainstexperimentalendocarditis.91
Inthelongerterm,suchstrategiescouldbemoreeffectivethanantimicrobial
prophylaxis,especiallyinhighcases.

InfectiveEndocarditisCausativeAgents:Drivers
forChangingEpidemiology
■AstheunderlyingriskfactorsforIEhavechanged
overthepast4decades,therehavebeenchangesin
theproportionofthemicrobialagentsresponsible.
■Therehasbeenareductioninrheumaticheart
diseaseindevelopedcountriesinparticular,witha
concomitantriseinsurvival,andsurgicalintervention

andmanagementofchildrenwithCHD.


■Heathcareinterventionsandincreasingsurvivalof
pretermneonatesandotherchildrenrequiringlongtermcentralvenousaccess(suchastreatmentof
malignancy)hasincreasedriskfactorsforIEinthe
absenceofCHD.
■Inadults,large-scaleepidemiologicstudieshave
demonstratedasignificantincreaseinstaphylococcal
spp.,bothS.aureusandso-calledcoagulase-negative
staphylococci(CONS),inkeepingwithchangingrisk
factorsoverthepast3to4decades.92
■Relativelyfewstudieshavelookedattheincidence
andchangesinriskfactorsandcausativeagentsin
children.Therehasbeenasimilartrendinincreasein
staphylococcalIEinthepastfewdecades.However,
onefactorthatmayhavedriventhisinadults,namely
intravenousdrugabuse,92isveryuncommonin
children.
CommentsonthecausativeagentsinpediatricIEandstudiesontheseare
summarizedinTables56.4and56.5.
Table56.4
CausativeAgentsandComments
CausativeAgent(s)
NotesandComments
Staphylococcusaureus
PredominantandoneofthemostvirulentcausesofIE.Associatedwithtissue
destructionandrootabscesses.
MorecommoninabsenceofCHD.
Highestmortalityrates,especiallyinneonates.

CoagulaseMorelikelytoaffectindwellingcardiacimplantssuchasshuntsandartificialvalves.
negative
Oftenassociatedwithindwellingcentralvenouslines,thoughcanbeimplantedat
staphylococci:
surgery.
S.epidermidis(most
CancauseNVE,butveryrareinchildrencomparedwithadults.